AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.METHODS: Freshly collected hepatocellular carcinoma(HCC...AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.METHODS: Freshly collected hepatocellular carcinoma(HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage Ⅲ primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS: The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo,P = 0.00121). After treatment, all patients in the study group had positive delayed hyper sensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO-and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.展开更多
BACKGROUND Fecal microbiota transplantation(FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clo...BACKGROUND Fecal microbiota transplantation(FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection(CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects. AIM To investigate the safety of FMT in children. METHODS A retrospective study was conducted on 49 patientswho underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events(AEs) related to FMT were divided into shortterm(48 h post-FMT) and long-term(3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS Forty-nine patients(mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32%(30/114). The most common shortterm AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age(P = 0.006) and immune state(P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo(P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence(P = 0.035), and the risk ratio in immunodeficient patients was 3.105(95%CI: 1.080-8.923).CONCLUSION Although FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children's long-term health is unpredictable.展开更多
AIM To investigate the effect of(-)-epigallocatechin-3-gallate(EGCG) on polyinosinic-polycytidylic acid(poly I:C)-triggered intracellular innate immunity against hepatitis C virus(HCV) in hepatocytes. METHODS A cell c...AIM To investigate the effect of(-)-epigallocatechin-3-gallate(EGCG) on polyinosinic-polycytidylic acid(poly I:C)-triggered intracellular innate immunity against hepatitis C virus(HCV) in hepatocytes. METHODS A cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain(JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular m RNAs and of intracellular and extracellular HCV RNA. Enzyme-linked immunosorbent assay was used to evaluate the interferon(IFN)-λ1 protein level in the cell culture supernatant. Immunostaining was used to examine HCV core protein expression in Huh7 cells.RESULTS Our recent study showed that HCV replication could impair poly I:C-triggered intracellular innate immune responses in hepatocytes. In the current study, we showed that EGCG treatment significantly increased the poly I:C-induced expression of Toll-like receptor 3(TLR3), retinoic acid-inducible gene I, and IFN-λ1 in JFH-1-Huh7 cells. In addition, supplementation with EGCG increased the poly I:C-mediated antiviral activity in JFH-1-Huh7 cells at the intracellular and extracellular HCV RNA and protein levels. Further investigation of the mechanisms showed that EGCG treatment significantly enhanced the poly I:C-induced expression of IFN-regulatory factor 9 and several antiviral IFNstimulated genes, including ISG15, ISG56, myxovirus resistance A, and 2'-5'-oligoadenylate synthetase 1, which encode the key antiviral elements in the IFN signaling pathway. CONCLUSION Our observations provide experimental evidence that EGCG has the ability to enhance poly I:C-induced intracellular antiviral innate immunity against HCV replication in hepatocytes.展开更多
AIM: To investigate the relationship between the superoxide dismutase (SOD), malondialdehyde (MDA)metabolic changes and the gastric carcinogenesis.METHODS: The SOD activity and MDA content were measured in the gastric...AIM: To investigate the relationship between the superoxide dismutase (SOD), malondialdehyde (MDA)metabolic changes and the gastric carcinogenesis.METHODS: The SOD activity and MDA content were measured in the gastric tissues from the focus center,peripheral and far-end areas of gastric carcinoma (n = 52)and gastric ulcer (n = 10). All the tissues were subjected to routine histological examinations and classifications.RESULTS: The SOD activity was greatly reduced but the MDA content was markedly increased in the center areas of the non-mucous gastric carcinoma (non-MGC); and the poorly differentiated gastric carcinoma varied. The SOD activity was gradually decreased and the MDA content was gradually increased in the tissues from the focus far-end, peripheral to center areas of non-MGC. Both of the SOD activity and the MDA content were significantly declined and were respectively at same low level in the tissues from the focus center, peripheral, and far-end area with the mucous gastric carcinoma (MGC). In contrast to the gastric ulcer and grade Ⅰ or Ⅱ of non-MGC, the same level of the SOD activity and the MDA content were found in the focus center areas. Between non-lvlGC (groups A-D) and gastric ulcer (group F), the differences of SOD activity and MDA content were very noticeable in the gastric tissues from the focus peripheral and far-end areas, in which the SOD activity showed noticeable increase and the MDA content showed noticeable decrease in the gastric ulcer.CONCLUSION: The active free radical reaction in the gastric tissues can induce the carcinogenesis of non-MGC.The utmost low ability of antioxidation in the gastric tissues can induce the carcinogenesis of MGC. The metabolic change of the free radicals centralized mostly in the center of ulcerated lesions only, which suggested the ability of antioxidation was declined only in these lesions. However,the metabolism of free radicals varied significantly and the ability of antioxidation declined not only in the local focus area but also in the abroad gastric tissues with gastric carcinoma.展开更多
BACKGROUND Congenital hepatic fibrosis(CHF)is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts.CHF is generally accompanied by a variety of co...BACKGROUND Congenital hepatic fibrosis(CHF)is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts.CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement.CASE SUMMARY We report a 5-year-4-month-old Chinese boy with congenital hypothyroidism(CH)diagnosed with CHF.The patient was diagnosed with CH by a newborn screening test and has since been taking levothyroxine.He has developed normally without neurocognitive deficits.Abnormal liver function was observed in the patient at the age of 4 years and 11 mo,and elevated levels of liver function indices were persistent for 5 mo.Radiological imaging indicated hepatosplenomegaly without narrowing of the portal vein but dilated splenic vein.A liver biopsy confirmed the pathological features of CHF.Genetic testing revealed two novel homozygous mutations,namely,c.2141-3T>C variant in PKHD1 related to CHF and c.2921G>A(p.R974H)in DUOX2 related to CH.The patient was treated with compound glycyrrhizin tablet,ursodeoxycholic acid,and levothyroxine after diagnosis.The patient achieved a favorable clinical outcome during a follow-up period of over 2 years.CONCLUSION Herein,we report the first case of a Chinese boy with comorbidity of CHF and CH,carrying both PKHD1 gene and DUOX2 gene novel mutations.Liver biopsy and genetic testing should be considered for the diagnosis of coexistent liver disease in CH patients with unexplained abnormal liver function.展开更多
Water electrolysis has been regarded as a promising technology to produce clean hydrogen fuel with high purity. However, large-scale water electrolysis has been greatly hindered due to the lack of non-noble metal cata...Water electrolysis has been regarded as a promising technology to produce clean hydrogen fuel with high purity. However, large-scale water electrolysis has been greatly hindered due to the lack of non-noble metal catalysts with high catalytic performance. Benefitting from unique hollow structures with large surface area and adjustable chemical compositions, hollow design plays an important role in improving the electrocatalytic performance for hydrogen evolution reaction(HER). Herein, we report an effective multi-step strategy to prepare hierarchical Co-decorated Mo_(2)C hollow spheres(CMCHSs) as electrocatalyst for HER. To be specific, the preparation process involves a metal-chelated polymerization and a subsequent surface modulation process. Owing to the unique hollow structure and incorporation of Co species,the as-prepared CMCHSs demonstrate largely enhanced HER performance with a low overpotential of 139 mV at the current density of 10 m A·cm^(-2) and good cycling durability in acid. The present research work highlights a new feasible strategy for the design of HER electrocatalyst via hollow designs and surface engineering.展开更多
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.METHODS: Freshly collected hepatocellular carcinoma(HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage Ⅲ primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS: The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo,P = 0.00121). After treatment, all patients in the study group had positive delayed hyper sensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO-and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.
基金Supported by Shanghai Hospital Development Center New Frontier Technology Joint Research Project,No.SHDC12017115
文摘BACKGROUND Fecal microbiota transplantation(FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection(CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects. AIM To investigate the safety of FMT in children. METHODS A retrospective study was conducted on 49 patientswho underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events(AEs) related to FMT were divided into shortterm(48 h post-FMT) and long-term(3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS Forty-nine patients(mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32%(30/114). The most common shortterm AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age(P = 0.006) and immune state(P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo(P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence(P = 0.035), and the risk ratio in immunodeficient patients was 3.105(95%CI: 1.080-8.923).CONCLUSION Although FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children's long-term health is unpredictable.
基金Supported by the National Natural Science Foundation of China,No.81500449the Natural Science Foundation of Shanghai,No.14ZR1434200+2 种基金Shanghai Municipal Commission of Health and Family Planning,No.20144Y0175the Scientific Research Foundation for the Returned Overseas Chinese Scholarsthe State Education Ministry of China,No.20150909-6
文摘AIM To investigate the effect of(-)-epigallocatechin-3-gallate(EGCG) on polyinosinic-polycytidylic acid(poly I:C)-triggered intracellular innate immunity against hepatitis C virus(HCV) in hepatocytes. METHODS A cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain(JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular m RNAs and of intracellular and extracellular HCV RNA. Enzyme-linked immunosorbent assay was used to evaluate the interferon(IFN)-λ1 protein level in the cell culture supernatant. Immunostaining was used to examine HCV core protein expression in Huh7 cells.RESULTS Our recent study showed that HCV replication could impair poly I:C-triggered intracellular innate immune responses in hepatocytes. In the current study, we showed that EGCG treatment significantly increased the poly I:C-induced expression of Toll-like receptor 3(TLR3), retinoic acid-inducible gene I, and IFN-λ1 in JFH-1-Huh7 cells. In addition, supplementation with EGCG increased the poly I:C-mediated antiviral activity in JFH-1-Huh7 cells at the intracellular and extracellular HCV RNA and protein levels. Further investigation of the mechanisms showed that EGCG treatment significantly enhanced the poly I:C-induced expression of IFN-regulatory factor 9 and several antiviral IFNstimulated genes, including ISG15, ISG56, myxovirus resistance A, and 2'-5'-oligoadenylate synthetase 1, which encode the key antiviral elements in the IFN signaling pathway. CONCLUSION Our observations provide experimental evidence that EGCG has the ability to enhance poly I:C-induced intracellular antiviral innate immunity against HCV replication in hepatocytes.
基金Supported by the Youth Science Fund of Guangdong Province Medicine and Hygiene, No. B19960095
文摘AIM: To investigate the relationship between the superoxide dismutase (SOD), malondialdehyde (MDA)metabolic changes and the gastric carcinogenesis.METHODS: The SOD activity and MDA content were measured in the gastric tissues from the focus center,peripheral and far-end areas of gastric carcinoma (n = 52)and gastric ulcer (n = 10). All the tissues were subjected to routine histological examinations and classifications.RESULTS: The SOD activity was greatly reduced but the MDA content was markedly increased in the center areas of the non-mucous gastric carcinoma (non-MGC); and the poorly differentiated gastric carcinoma varied. The SOD activity was gradually decreased and the MDA content was gradually increased in the tissues from the focus far-end, peripheral to center areas of non-MGC. Both of the SOD activity and the MDA content were significantly declined and were respectively at same low level in the tissues from the focus center, peripheral, and far-end area with the mucous gastric carcinoma (MGC). In contrast to the gastric ulcer and grade Ⅰ or Ⅱ of non-MGC, the same level of the SOD activity and the MDA content were found in the focus center areas. Between non-lvlGC (groups A-D) and gastric ulcer (group F), the differences of SOD activity and MDA content were very noticeable in the gastric tissues from the focus peripheral and far-end areas, in which the SOD activity showed noticeable increase and the MDA content showed noticeable decrease in the gastric ulcer.CONCLUSION: The active free radical reaction in the gastric tissues can induce the carcinogenesis of non-MGC.The utmost low ability of antioxidation in the gastric tissues can induce the carcinogenesis of MGC. The metabolic change of the free radicals centralized mostly in the center of ulcerated lesions only, which suggested the ability of antioxidation was declined only in these lesions. However,the metabolism of free radicals varied significantly and the ability of antioxidation declined not only in the local focus area but also in the abroad gastric tissues with gastric carcinoma.
基金Supported by National Natural Science Foundation of China,No.81870373Shanghai Hospital Development Center New Frontier Technology Joint Research Project,No.SHDC12017115and 2019 Shanghai“Innovative Action Plan of Science and Technology”Animal Research Project Guide,No.19140904301.
文摘BACKGROUND Congenital hepatic fibrosis(CHF)is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts.CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement.CASE SUMMARY We report a 5-year-4-month-old Chinese boy with congenital hypothyroidism(CH)diagnosed with CHF.The patient was diagnosed with CH by a newborn screening test and has since been taking levothyroxine.He has developed normally without neurocognitive deficits.Abnormal liver function was observed in the patient at the age of 4 years and 11 mo,and elevated levels of liver function indices were persistent for 5 mo.Radiological imaging indicated hepatosplenomegaly without narrowing of the portal vein but dilated splenic vein.A liver biopsy confirmed the pathological features of CHF.Genetic testing revealed two novel homozygous mutations,namely,c.2141-3T>C variant in PKHD1 related to CHF and c.2921G>A(p.R974H)in DUOX2 related to CH.The patient was treated with compound glycyrrhizin tablet,ursodeoxycholic acid,and levothyroxine after diagnosis.The patient achieved a favorable clinical outcome during a follow-up period of over 2 years.CONCLUSION Herein,we report the first case of a Chinese boy with comorbidity of CHF and CH,carrying both PKHD1 gene and DUOX2 gene novel mutations.Liver biopsy and genetic testing should be considered for the diagnosis of coexistent liver disease in CH patients with unexplained abnormal liver function.
基金financially supported by the National Natural Science Foundation of China (No.51902016)the Fundamental Research Funds for the Central Universities (Nos.buctrc201829 and buctrc201904)the "Double-First Class" Construction Projects (No.XK1804-02)。
文摘Water electrolysis has been regarded as a promising technology to produce clean hydrogen fuel with high purity. However, large-scale water electrolysis has been greatly hindered due to the lack of non-noble metal catalysts with high catalytic performance. Benefitting from unique hollow structures with large surface area and adjustable chemical compositions, hollow design plays an important role in improving the electrocatalytic performance for hydrogen evolution reaction(HER). Herein, we report an effective multi-step strategy to prepare hierarchical Co-decorated Mo_(2)C hollow spheres(CMCHSs) as electrocatalyst for HER. To be specific, the preparation process involves a metal-chelated polymerization and a subsequent surface modulation process. Owing to the unique hollow structure and incorporation of Co species,the as-prepared CMCHSs demonstrate largely enhanced HER performance with a low overpotential of 139 mV at the current density of 10 m A·cm^(-2) and good cycling durability in acid. The present research work highlights a new feasible strategy for the design of HER electrocatalyst via hollow designs and surface engineering.
